Mercury concentrations in hair from populations in Wau-Bulolo area, Papua New Guinea

Total mercury (Hg) concentrations were determined in scalp hair from the populations in the Wau-Bulolo area, eastern Papua New Guinea (PNG), where humans are exposed to large quantities of Hg through gold-mining activities by Hg amalgamation processes. Humans living upstream and not engaged in gold mining had a mean hair Hg concentration of 0.55 g g^–1 (range: 0.19–1.1 g g^–1) (n=80), which was recognized as the background level in this area. In contrast, the populations involved in gold-mining activities had a significantly higher level of hair Hg (mean: 1.2 g g^–1, range: 0.39–3.0 g g^–1) (n=86) than the background level, indicating direct or indirect exposure to Hg from gold mining. The hair Hg level in populations downstream of the gold-mining area was significantly higher than the background level, due to the consumption of Hg-contaminated fish. Mercury concentrations were significantly higher in males than in females, regardless of location properties.     

In vivo effects of some histamine H1-receptor antagonists on monoamine metabolism in the mouse brain

Summary The in vivo effects of four Hr-antagonists, diphenhydramine, chlorpheniramine, mepyramine, and promethazine, on the metabolism of noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were investigated in the whole mouse brain. Diphenhydramine and chlorpheniramine had no significant effect on levels of NA, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), DA, and 5-HT, but they significantly decreased levels of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). In particular chlorpheniramine markedly decreased 5-HIAA levels at doses as low as 1 mg/kg, i. p. Mepyramine significantly decreased 5-HIAA levels but not those of other substances. High doses of promethazine significantly decreased NA levels but markedly increased those of MHPG, DOPAC, HVA, 5-HT, and 5-HIAA. The DA reduction induced by -methyl-p-tyrosine (-MT) was significantly inhibited by diphenhydramine, chlorpheniramine, and promethazine, but the -MT-induced NA decrease was significantly enhanced by promethazine. The 5-HIAA accumulations induced by probenecid were significantly inhibited by chlorpheniramine and mepyramine. These results suggest: (1) Diphenhydramine and chlorpheniramine inhibit the turnover of both DA and 5-HT by blocking their neuronal uptake. (2) Promethazine and mepyramine inhibit DA and 5-HT turnover, respectively, as a result of the inhibition of the uptake mechanism. (3) Promethazine increases NA turnover by enhancing NA release. The discriminative effects of these drugs on the monoamine systems may be related to some differences in their CNS actions. Send offprint requests to K. Saeki at the above address     

Effects of isoflurane and halothane on the calcium ion-tension curve in rat myocardium

In order to clarify the interaction of volatile anesthetics and extracellular calcium ion on the myocardial contraction, effects of both isoflurane (1.0%) and halothane (0.5%) on the extracellular calcium ion concentration ([Ca²⁺]_O)-tension curve were studied. Increasing [Ca²⁺]_O enhanced the myocardial contraction response, and the maximal response was obtained at [Ca²⁺]_O of 3.0mM. Halothane depressed the maximal value of the tension development in response to increasing [Ca²⁺]_O, while isoflurane did not (P 0.01). The probit response of the developed tension to the changes in [Ca²⁺]_O indicated that isoflurane increased the median effective concentration (EC₅₀) of [Ca²⁺]_O significantly from 0.484 ± 0.051 (mean ± SEM) to 0.870 ± 0.056mM (P = 0.001), but halothane did not (P = 0.018). Therefore, 1.0% isoflurane was concluded to move the [Ca²⁺]_O-tension curve to the right, while a downwards shift occurred with 0.5% halothane.(Saeki S, Hirakawa M, Shimosato S: Effects of Isoflurane and Halothane on the Calcium Ion-tension Curve in Rat Myocardium. J Anesth 6: 172–175, 1992)     

Proliferation, Vascular Endothelial Growth Factor Expression and Cavernous Sinus Invasion in Growth Hormone Secreting Pituitary Adenomas

Summary  Surgical cure of growth hormone producing pituitary adenomas (GHomas) becomes difficult when they invade the cavernous sinus (CS). Tumour proliferative activity and angiogenesis are thought to be required for tumour growth and invasion, and vascular endothelial growth factor (VEGF) activates neovascularization around tumours. In this study, the mechanism and clinical significance of CS invasion is analysed. In 25 surgically treated GHomas, the extent of CS invasion was classified as high (Knosp's grade 3 and 4), and low (grade 0, 1 and 2) MR grades, and the MR grades were compared with tumour proliferative potential (Ki-67 expression), angiogenetic demand (VEGF expression), volume of adenomas and serum hormone levels.  The Ki-67 index of high MR grade adenomas (1.17±0.62%) was significantly higher than that of low MR grade adenomas (0.55±0.42%, p=0.027), whereas VEGF expression showed no significant correlation with MR grades (p>0.999). Tumour volume also showed a significant correlation with MR grade (p=0.002). VEGF expression was not correlated with serum hormone level and volume, but was correlated with tumour proliferative potential. Proliferative potential and tumour volume were two independent factors related to CS invasion. Although VEGF expression was not a direct factor related to CS invasion, it may indirectly play a role in activation of tumour aggressiveness, which is required in CS invasion.  Our results show that high MR grade adenomas have higher proliferative ability. In order to improve the surgical outcome, pre-operative medical debulking is indicated, particularly, in such adenomas.     

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.     

Pyoderma gangrenosum in an ulcerative colitis patient during treatment with vedolizumab responded favorably to adsorptive granulocyte and monocyte apheresis

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4β7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.     

Glucose and methionine uptake and proliferative activity in meningiomas

Abstract

Despite similar benign histological appearances, proliferative activity of meningiomas varies tumor to tumor, and even region to region in a tumor. To predict proliferative potential before surgery, we compared regional uptake of2-[18F]fluoro-2-deoxyglucose ([18F]FDC) and L-fmethyl-11 CJmethionine ([71C]MET) with histological indices of tumor proliferative activity in 17 specimens from six patients with meningioma obtained by PET guided stereotactic biopsies. Uptake of I11C]MET', an index of protein synthesis rate, significantly correlated not only with the count of nucleolar organizer regions (NORs), a histological index of protein synthesis, but also with Ki-67 index, a histological index of proliferative activity. On the other hand, [18F]FDC uptake showed no significant correlation with Ki-67 index or clinical malignancy. These results suggest that [11 C]MET-PET is a useful tool for predicting tumor proliferative potential in meningiomas. [Neurol Res 1999; 21: 640-644]